The formation of beta-amyloid (Aβ) plaques is a classical hallmark of Alzheimer's disease (AD) that is associated with the promotion of neuroinflammation and subsequent neurotoxicity. Given the limited therapeutic options for targeting and clearing Aβ plaques in AD, there is an urgent need to develop effective approaches to reduce plaque accumulation. The objective of this study was to validate mild magnetic nanoparticle (MNP) hyperthermia technology as a strategy to clear Aβ deposits and determine the impact on microglia functionality. Our results demonstrated that the heating of MNPs localized to Aβ aggregates upon exposure to high frequency alternating magnetic field (AMF) was sufficient to disrupt Aβ plaques, resulting in its fragmentation. Importantly, this could facilitate the phagocytic clearance of Aβ as well as attenuate pro-inflammatory responses by human microglial cells. Our results support the feasibility of mild MNP/AMF hyperthermia as a new strategy for reducing beta-amyloid burdens in Alzheimer's disease.

β-淀粉样蛋白 (Aβ) 斑块的形成是阿尔茨海默病 (AD) 的典型标志，与促进神经炎症和随后的神经毒性有关。鉴于靶向和清除 AD 中 Aβ 斑块的治疗选择有限，迫切需要开发有效的方法来减少斑块积聚。本研究的目的是验证温和磁性纳米粒子 (MNP) 热疗技术作为清除 Aβ 沉积物并确定对小胶质细胞功能影响的策略。我们的结果表明，在暴露于高频交变磁场 (AMF) 时，加热定位于 Aβ 聚集体的 MNP 足以破坏 Aβ 斑块，导致其碎裂。重要的，这可以促进 Aβ 的吞噬清除以及减弱人类小胶质细胞的促炎反应。我们的结果支持轻度 MNP/AMF 热疗作为减少阿尔茨海默病中 β-淀粉样蛋白负担的新策略的可行性。